KR20120073128A - Deuterated oligo ethylene glycol thiol molecule and method for preparing the same - Google Patents
Deuterated oligo ethylene glycol thiol molecule and method for preparing the same Download PDFInfo
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- KR20120073128A KR20120073128A KR1020110140499A KR20110140499A KR20120073128A KR 20120073128 A KR20120073128 A KR 20120073128A KR 1020110140499 A KR1020110140499 A KR 1020110140499A KR 20110140499 A KR20110140499 A KR 20110140499A KR 20120073128 A KR20120073128 A KR 20120073128A
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- ethoxy
- ethanol
- enyloxy
- undec
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- -1 ethylene glycol thiol Chemical class 0.000 title claims abstract description 21
- 238000000034 method Methods 0.000 title claims description 11
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 title abstract description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 12
- 239000000243 solution Substances 0.000 claims abstract description 11
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 claims abstract description 10
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 9
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims abstract description 8
- 229910052805 deuterium Inorganic materials 0.000 claims abstract description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims abstract description 7
- RGCODMYUZUDYDG-GBIJOAKOSA-N 1,1,2,2-tetradeuterio-2-[2-(2-hex-5-enoxyethoxy)ethoxy]ethanol Chemical compound C(CCCC=C)OCCOCCOC(C(O)([2H])[2H])([2H])[2H] RGCODMYUZUDYDG-GBIJOAKOSA-N 0.000 claims abstract description 5
- SNQQBXFXPDCEIT-IWFQOFTGSA-N 1,1,2,2-tetradeuterio-2-[2-(2-undec-10-enoxyethoxy)ethoxy]ethanol Chemical compound C(CCCCCCCCC=C)OCCOCCOC(C(O)([2H])[2H])([2H])[2H] SNQQBXFXPDCEIT-IWFQOFTGSA-N 0.000 claims abstract description 5
- ZFHKAEQCLIWJHF-CWUGWKFWSA-N 1,1,2,2-tetradeuterio-2-[2-[2-(6-sulfanylhexoxy)ethoxy]ethoxy]ethanol Chemical compound SCCCCCCOCCOCCOC(C(O)([2H])[2H])([2H])[2H] ZFHKAEQCLIWJHF-CWUGWKFWSA-N 0.000 claims abstract description 5
- RZNFQLKSJIBASQ-UHFFFAOYSA-N 6-[2-(2-bromoethoxy)ethoxy]hex-1-ene Chemical compound BrCCOCCOCCCCC=C RZNFQLKSJIBASQ-UHFFFAOYSA-N 0.000 claims abstract description 5
- LYCAIKOWRPUZTN-LNLMKGTHSA-N 1,1,2,2-tetradeuterioethane-1,2-diol Chemical compound [2H]C([2H])(O)C([2H])([2H])O LYCAIKOWRPUZTN-LNLMKGTHSA-N 0.000 claims abstract description 4
- WBMLSMQYONHTHF-UHFFFAOYSA-N 2-(2-hex-5-enoxyethoxy)ethanol Chemical compound C(CCCC=C)OCCOCCO WBMLSMQYONHTHF-UHFFFAOYSA-N 0.000 claims abstract description 4
- VTQOXUJZSLYUQC-UHFFFAOYSA-N 2-(2-undec-10-enoxyethoxy)ethanol Chemical compound C(CCCCCCCCC=C)OCCOCCO VTQOXUJZSLYUQC-UHFFFAOYSA-N 0.000 claims abstract description 4
- FASSFROSROBIBE-UHFFFAOYSA-N 2-[2-[2-(11-sulfanylundecoxy)ethoxy]ethoxy]ethanol Chemical compound OCCOCCOCCOCCCCCCCCCCCS FASSFROSROBIBE-UHFFFAOYSA-N 0.000 claims abstract description 4
- GAVVRGAPJXHTRL-UHFFFAOYSA-N 11-[2-(2-bromoethoxy)ethoxy]undec-1-ene Chemical compound BrCCOCCOCCCCCCCCCC=C GAVVRGAPJXHTRL-UHFFFAOYSA-N 0.000 claims abstract description 3
- RIMXEJYJXDBLIE-UHFFFAOYSA-N 6-bromohex-1-ene Chemical compound BrCCCCC=C RIMXEJYJXDBLIE-UHFFFAOYSA-N 0.000 claims abstract description 3
- LXEKPEMOWBOYRF-UHFFFAOYSA-N [2-[(1-azaniumyl-1-imino-2-methylpropan-2-yl)diazenyl]-2-methylpropanimidoyl]azanium;dichloride Chemical compound Cl.Cl.NC(=N)C(C)(C)N=NC(C)(C)C(N)=N LXEKPEMOWBOYRF-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000011259 mixed solution Substances 0.000 claims abstract 2
- 238000004949 mass spectrometry Methods 0.000 claims description 16
- 150000003573 thiols Chemical class 0.000 claims description 13
- 150000001875 compounds Chemical class 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 6
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 5
- DCTOHCCUXLBQMS-UHFFFAOYSA-N 1-undecene Chemical compound CCCCCCCCCC=C DCTOHCCUXLBQMS-UHFFFAOYSA-N 0.000 claims description 4
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims description 4
- MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 claims description 3
- KGRFJZNUVNEHIJ-UHFFFAOYSA-N acetic acid;ethanethioic s-acid Chemical compound CC(O)=O.CC(S)=O KGRFJZNUVNEHIJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims 1
- 238000003756 stirring Methods 0.000 claims 1
- 238000004458 analytical method Methods 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 239000013558 reference substance Substances 0.000 abstract description 3
- YPLVPFUSXYSHJD-UHFFFAOYSA-N 11-bromoundec-1-ene Chemical compound BrCCCCCCCCCC=C YPLVPFUSXYSHJD-UHFFFAOYSA-N 0.000 abstract description 2
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 abstract description 2
- VYMPLPIFKRHAAC-UHFFFAOYSA-N 1,2-ethanedithiol Chemical compound SCCS VYMPLPIFKRHAAC-UHFFFAOYSA-N 0.000 abstract 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 abstract 1
- YDADHEIFTCDFFX-UHFFFAOYSA-N s-[11-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]undecyl] ethanethioate Chemical compound CC(=O)SCCCCCCCCCCCOCCOCCOCCO YDADHEIFTCDFFX-UHFFFAOYSA-N 0.000 abstract 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- 239000000090 biomarker Substances 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 11
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 11
- 229910052737 gold Inorganic materials 0.000 description 11
- 239000010931 gold Substances 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 238000001514 detection method Methods 0.000 description 7
- 239000002105 nanoparticle Substances 0.000 description 7
- 239000013545 self-assembled monolayer Substances 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000011159 matrix material Substances 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 238000005227 gel permeation chromatography Methods 0.000 description 5
- 238000004445 quantitative analysis Methods 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- LFQSCWFLJHTTHZ-LNLMKGTHSA-N 1,1,2,2-tetradeuterioethanol Chemical compound [2H]C([2H])C([2H])([2H])O LFQSCWFLJHTTHZ-LNLMKGTHSA-N 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 230000002596 correlated effect Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- FASSFROSROBIBE-HKWZOHSCSA-N 1,1,2,2-tetradeuterio-2-[2-[2-(11-sulfanylundecoxy)ethoxy]ethoxy]ethanol Chemical compound SCCCCCCCCCCCOCCOCCOC(C(O)([2H])[2H])([2H])[2H] FASSFROSROBIBE-HKWZOHSCSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 210000002307 prostate Anatomy 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000002094 self assembled monolayer Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 description 2
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- 235000013980 iron oxide Nutrition 0.000 description 2
- VBMVTYDPPZVILR-UHFFFAOYSA-N iron(2+);oxygen(2-) Chemical class [O-2].[Fe+2] VBMVTYDPPZVILR-UHFFFAOYSA-N 0.000 description 2
- 239000011859 microparticle Substances 0.000 description 2
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 239000002096 quantum dot Substances 0.000 description 2
- 239000012925 reference material Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- CZZZWEDUOMBCQE-UHFFFAOYSA-N 1-bromoundec-1-ene Chemical compound CCCCCCCCCC=CBr CZZZWEDUOMBCQE-UHFFFAOYSA-N 0.000 description 1
- XLEYFDVVXLMULC-UHFFFAOYSA-N 2',4',6'-trihydroxyacetophenone Chemical compound CC(=O)C1=C(O)C=C(O)C=C1O XLEYFDVVXLMULC-UHFFFAOYSA-N 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- HOPBXSLGFVTEFD-UHFFFAOYSA-N C(C)(OCCCCCCCCCCC)=S Chemical compound C(C)(OCCCCCCCCCCC)=S HOPBXSLGFVTEFD-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 101100377506 Drosophila melanogaster 14-3-3zeta gene Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 1
- HATRDXDCPOXQJX-UHFFFAOYSA-N Thapsigargin Natural products CCCCCCCC(=O)OC1C(OC(O)C(=C/C)C)C(=C2C3OC(=O)C(C)(O)C3(O)C(CC(C)(OC(=O)C)C12)OC(=O)CCC)C HATRDXDCPOXQJX-UHFFFAOYSA-N 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
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- 238000003745 diagnosis Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
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- 239000000463 material Substances 0.000 description 1
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- 102000004169 proteins and genes Human genes 0.000 description 1
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- 210000002966 serum Anatomy 0.000 description 1
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- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000001269 time-of-flight mass spectrometry Methods 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C321/00—Thiols, sulfides, hydropolysulfides or polysulfides
- C07C321/02—Thiols having mercapto groups bound to acyclic carbon atoms
- C07C321/08—Thiols having mercapto groups bound to acyclic carbon atoms of an acyclic unsaturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/06—Separation; Purification; Stabilisation; Use of additives
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/62—Detectors specially adapted therefor
- G01N30/72—Mass spectrometers
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Abstract
Description
본 발명은 중수소로 치환된 올리고에틸렌티올 분자 및 그 제조방법에 관한 것이다.The present invention relates to oligoethylene thiol molecules substituted with deuterium and a method of preparing the same.
최근 생물학적, 의학적 검체 내에 극미량으로 존재하는 일종의 생체분자 (DNA, 단백질, 펩타이드, 지질 등) 인 질병 바이오 마커의 구조나 농도의 정성적, 정량적 변화를 분석함으로서 질병의 진단 및 진행상태, 약물의 치료효과, 다른 질병과의 연관성을 종합적으로 판단하기 위해 학계에서 다양한 연구가 이루어지고 있다. Diagnosis and progress of disease and treatment of drugs by analyzing qualitative and quantitative changes in the structure or concentration of disease biomarkers, which are a kind of biomolecules (DNA, proteins, peptides, lipids, etc.) present in trace amounts in biological and medical samples. Various studies are being conducted in academia to comprehensively determine the effects and associations with other diseases.
이 중에서도 질병의 진행 상태 및 치료효과를 알기 위한 바이오 마커의 정량적 분석의 필요성이 커지고 있다. 이런 바이오 마커의 정량적 분석을 위한 학계의 다양한 연구 중에서도 질량분석기 (MALDI-TOF MS) 를 이용한 분석은 낮은 농도의 검출 한계, 높은 민감도 및 빠른 분석 시간 등의 장점을 갖고 있어 많은 사용이 되고 있다. 하지만 표적 분자의 정확한 양에 대한 정보까지 알기 위해서는 현재 사용 되는 MALDI-TOF 방법 만으로는 어려운 점이 있다.Among them, the necessity of quantitative analysis of biomarkers for knowing the progress of disease and the therapeutic effect is increasing. Among the various studies of the academic community for the quantitative analysis of such biomarkers, the analysis using mass spectrometer (MALDI-TOF MS) has many advantages because it has the advantages of low detection limit, high sensitivity and fast analysis time. However, in order to know the exact amount of the target molecule, the current MALDI-TOF method is difficult.
다른 한편으로 바이오 마커의 정량적 분석을 위해서 본 발명에서는 분석 대상 시료를 금 표면에 고정 시킬 수 있는 자가조립 단분자층을 이용한 분석 시스템이 사용된다. 금-황 간의 공유결합으로 고정되어 있는 자가조립 단분자 층은 다양한 바이오마커의 활성 그룹과 반응하여 금 표면에 고정될 수 있으며, 표적 분자가 고정되어 있는 자가조립 단분자층을 MALDI-TOF를 이용하여 분석해 검출이 가능하다. 하지만 표적분자의 정확한 절대량을 알기 위해서는 기준 물질이 필요하며, 그 기준물질은 표적 분자와 분자량은 다르지만 물리/화학적 특성이 동일하여야 한다. On the other hand, for the quantitative analysis of the biomarker, the present invention uses an analysis system using a self-assembled monolayer which can fix the sample to be analyzed on the gold surface. The self-assembled monolayer, which is immobilized by covalent bonds between gold and sulfur, can be immobilized on the surface of gold by reacting with active groups of various biomarkers. Detection is possible. However, in order to know the exact absolute amount of the target molecule, a reference substance is required, and the reference substance must have the same physical and chemical properties but different molecular weight from the target molecule.
관련 선행특허로 대한민국특허공개번호 제1020090068199호는 '질량 분광법에 의한 바이오마커 어세이'에 관한 것으로, 샘플 중에 하나 이상의 폴리펩티드 바이오마커가 존재하는 지를 결정하는 방법을 제공하며, 이러한 방법은, (a) 샘플을 질량 분광 (MS) 분석하고, 검출된 각각의 신호에 대한 체류 시간 지수 및 상응하는 질량을 기록하는 단계; (b) 각각의 신호에 상응하는 질량을 바이오마커 질량의 참조 데이터베이스와 상호관련시켜서 각각의 신호와 참조 바이오마커 사이의 상관관계를 형성하고, 질량이 참조 바이오마커 질량과 상호관련되지 않는 신호를 폐기하는 단계; (c) 질량이 참조 바이오마커와 상호관련되는 신호를 저장하는 단계; (d) 유사성 척도를 이용하여 각각의 신호의 MS 스펙트럼을 데이터베이스내의 참조 바이오마커의 MS 스펙트럼과 매칭시킴으로써 각각의 저장된 신호와 참조 바이오마커 사이의 상관관계를 확정하여 포지티브하게 상호관련되는 일련의 신호를 한정하는 단계; (e) 각각의 포지티브하게 상호관련되는 신호의 세기를 측정하고, 판별 함수를 이용하여 이의 절대 신호 세기 또는 이의 상대 신호 세기를 점수화하는 단계; (f) 한계치를 판별 함수로부터 수득된 점수값에 적용하여 바이오마커의 존재 여부를 결정하는 단계를 포함한다고 기재되어 있으며,As a related prior patent, Korean Patent Publication No. 1020090068199 relates to a 'biomarker assay by mass spectrometry', and provides a method of determining whether one or more polypeptide biomarkers are present in a sample. ) Mass spectrometric (MS) analysis of the sample and recording the retention time index and corresponding mass for each detected signal; (b) correlating the mass corresponding to each signal with a reference database of biomarker masses to form a correlation between each signal and the reference biomarker and discard signals whose mass is not correlated with the reference biomarker mass. Making; (c) storing a signal whose mass is correlated with a reference biomarker; (d) Matching the MS spectrum of each signal with the MS spectrum of the reference biomarker in the database using the similarity measure to establish a correlation between each stored signal and the reference biomarker to produce a positively correlated series of signals. Defining step; (e) measuring the strength of each positively correlated signal and scoring its absolute signal strength or its relative signal strength using a discriminant function; (f) applying a threshold to a score obtained from a discriminant function to determine the presence of a biomarker,
다른 관련 선행특허로 대한민국특허공개번호 제1020030066672호는 '전립선 특이성 막 항원 및 기타 전립선 마커의 정량 검출방법 및 장치'에 관한 것으로, PSMA, PSMA'의 검출 및 정량 및 전립선 암, 양성 전립선 과다형성 및 음성 진단을 차별화하는 데에 사용하기 위한 다른 샘플 형 뿐 아니라 혈청 샘플의 다른 전립선 마커를 기재하고 있다.As another related prior patent, Korean Patent Publication No. 1020030066672 relates to a method and apparatus for quantitative detection of prostate specific membrane antigens and other prostate markers, and the detection and quantification of PSMA, PSMA and prostate cancer, benign prostatic hyperplasia and Other prostate markers of serum samples are described as well as other sample types for use in differentiating negative diagnoses.
본 발명은 상기의 문제점을 해결하고, 상기의 필요성에 의하여 안출된 것으로서 본 발명의 목적은 바이오마커의 정량적 분석을 위한 화합물을 제공하는 것이다.The present invention solves the above problems, and the object of the present invention is to provide a compound for the quantitative analysis of biomarkers.
본 발명의 다른 목적은 상기 화합물을 제조하는 방법을 제공하는 것이다.Another object of the present invention is to provide a method for preparing the compound.
상기의 목적을 달성하기 위하여 본 발명은 하기 화학식 1에 기재된 중수소로 치환된 티올 분자를 제공한다.In order to achieve the above object, the present invention provides a thiol molecule substituted with deuterium represented by the formula (1).
[화학식 1][Formula 1]
여기서, l은 0~9의 정수, m은 0 이상 의 정수이고, n은 1 이상의 정수이며, m과 n의 합은 3, 4, 5 또는 6을 만족하여야 한다. Where l is an integer of 0 to 9, m is an integer of 0 or more, n is an integer of 1 or more, and the sum of m and n must satisfy 3, 4, 5 or 6.
하기 화학식 1에 기재된 중수소로 치환된 티올 분자:Thiol molecules substituted with deuterium as described in Formula 1:
[화학식 1][Formula 1]
여기서, l은 0~9의 정수, m은 0 이상의 정수이고, n은 1 이상의 정수이며, m과 n의 합은 3, 4, 5 또는 6을 만족하여야 한다. Where l is an integer of 0 to 9, m is an integer of 0 or more, n is an integer of 1 or more, and the sum of m and n must satisfy 3, 4, 5 or 6.
본 발명의 일 구현예에 있어서, 상기 화학식 1의 l은 4 또는 9, m과 n의 합은 3, 4, 5 또는 6인 것이 바람직하나 이에 한정되지 아니한다.In one embodiment of the present invention, 1 in Formula 1 is 4 or 9, and the sum of m and n is preferably 3, 4, 5 or 6, but is not limited thereto.
도 6에서 알 수 있는 바와 같이, 본 발명에서 상기 화학식 1의 l은 0에서 9까지 모두 가능하며, 따라서 본 발명의 화학식 1의 화합물의 알킬 체인의 탄소수는 2에서 11까지가 가능하나 이에 한정되지 아니한다.As can be seen in Figure 6, in the present invention, l of Formula 1 may be all from 0 to 9, so the carbon number of the alkyl chain of the compound of
또한 본 발명은 a)NaOH 용액 및 다이에틸렌 글라이콜의 혼합액에 6-브로모헥센 또는 11-브로모운데센(bromoundecene)을 첨가하고 반응시켜서 2-(2-(hex-5-enyloxy)ethoxy)ethanol 또는 2-(2-(undec-10-enyloxy)ethoxy)ethanol을 합성하는 단계;b)상기 2-(2-(hex-5-enyloxy)ethoxy)ethanol 또는 2-(2-(undec-10-enyloxy)ethoxy)ethanol에 트리페닐 포스핀(triphenyl phosphine) 첨가하여 교반하고 카본테트라브로마이드(cartetrabonbromide)를 첨가하고 반응시켜서 6-(2-(2-bromoethoxy)ethoxy)hex-1-ene 또는 11-(2-(2-bromo- ethoxy)ethoxy)undec-1-ene 을 합성하는 단계; c)6-(2-(2-bromoethoxy)ethoxy)hex-1-ene 또는 11-(2-(2-bromo- ethoxy)ethoxy)undec-1-ene 용액에 NaH 및 에틸렌글리콜-D4를 첨가하고 반응시켜서 2-(2-(2-(hex-5-enyloxy)ethoxy)ethoxy)ethanol-d4 또는 2-(2-(2-(undec-10-enyloxy)ethoxy)ethoxy)ethanol-d4를 합성하는 단계; d)2-(2-(2-(hex-5-enyloxy)ethoxy)ethoxy)ethanol-d4 또는 2-(2-(2-(undec-10-enyloxy)ethoxy)ethoxy)ethanol-d4 용액에 티오아세트산(Thioacetic acid) 및 AMPA(2,2'-azobis(2-methylpropionamidine)dihydrochloride)를 가하고 반응시켜서 S-6-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)hexyl ethanethioate-d4 또는 S-11-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)undecyl ethanethioate를 합성하는 단계;및 e)S-6-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)hexyl ethanethioate-d4 또는 S-11-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)undecyl ethanethioate 용액에 HCl를 첨가하여 반응한 후 정제하여 2-(2-(2-(6-mercaptohexyloxy)ethoxy)ethoxy)ethanol-d4 또는 2-(2-(2-(11-mercaptoundecyloxy)ethoxy)ethoxy)ethanol을 합성하는 단계를 포함하는 상기 화학식 1의 화합물 제조방법을 제공한다.In addition, the present invention is a) a mixture of a) NaOH solution and diethylene glycol 6-bromohexene or 11-bromooundene (bromoundecene) by adding and reacting 2- (2- (hex-5-enyloxy) ethoxy ) Synthesizing ethanol or 2- (2- (undec-10-enyloxy) ethoxy) ethanol; b) The 2- (2- (hex-5-enyloxy) ethoxy) ethanol or 2- (2- (undec- Triphenyl phosphine was added to 10-enyloxy) ethoxy) ethanol, stirred, carbon tetrabromide was added and reacted to react with 6- (2- (2-bromoethoxy) ethoxy) hex-1-ene or 11 Synthesizing-(2- (2-bromoethoxy) ethoxy) undec-1-ene; c) Add NaH and ethylene glycol-D4 to a 6- (2- (2-bromoethoxy) ethoxy) hex-1-ene or 11- (2- (2-bromoethoxy) ethoxy) undec-1-ene solution Reacting to synthesize 2- (2- (2- (hex-5-enyloxy) ethoxy) ethoxy) ethanol-d4 or 2- (2- (2- (undec-10-enyloxy) ethoxy) ethoxy) ethanol-d4 step; d) 2- (2- (2- (2- (hex-5-enyloxy) ethoxy) ethoxy) ethanol-d4 or 2- (2- (2- (undec-10-enyloxy) ethoxy) ethoxy) ethanol-d4 in solution Acetic acid (Thioacetic acid) and AMPA (2,2'-azobis (2-methylpropionamidine) dihydrochloride) are added and reacted to give S-6- (2- (2- (2-hydroxyethoxy) ethoxy) ethoxy) hexyl ethanethioate-d4 or S Synthesizing -11- (2- (2- (2-hydroxyethoxy) ethoxy) ethoxy) undecyl ethanethioate; and e) S-6- (2- (2- (2-hydroxyethoxy) ethoxy) ethoxy) hexyl ethanethioate- HCl is added to the d4 or S-11- (2- (2- (2-hydroxyethoxy) ethoxy) ethoxy) undecyl ethanethioate solution, followed by purification to obtain 2- (2- (2- (6-mercaptohexyloxy) ethoxy) ethoxy It provides a method for preparing a compound of
본 발명의 일 구현예에 있어서 상기 본 발명의 제조방법은 n이 2이상인 경우 d)단계 이전에 상기 b)단계와 c)단계를 반복하는 단계를 포함하는 것이 바람직하다.In one embodiment of the present invention, the manufacturing method of the present invention preferably includes repeating steps b) and c) before step d) when n is 2 or more.
또한 본 발명은 상기 화학식 1의 화합물을 유효성분으로 포함하는 질량분석용 조성물을 제공한다.In another aspect, the present invention provides a composition for mass spectrometry comprising the compound of
이하 본 발명을 설명한다. Hereinafter, the present invention will be described.
상기 화학식 1에서 제시한 티올분자는 알킬사슬의 길이, 중수소화된 에틸렌 글리콜, 중수소화 되지 않은 에틸렌 글리콜의 수에 따라 (화학식 1의 l, m, n의 조합에 따라) 다양한 형태를 가질 수 있다. 대표적인 합성방법은 도 1과 2와 같다.The thiol molecule represented by Chemical Formula 1 may have various forms (depending on the combination of l, m and n of Chemical Formula 1) depending on the length of the alkyl chain, the deuterated ethylene glycol and the number of undeuterated ethylene glycol. . Representative synthetic methods are shown in FIGS. 1 and 2.
상기 본 발명의 화합물은 질량분석 기준물질로 사용되며 많은 부분에서 응용가능하며, 다음과 같은 사용 예를 제시한다.The compound of the present invention is used as a mass spectrometry reference material and can be applied in many parts, and the following use examples are given.
1)정량분석을 위한 내위 기준물질(Internal Standard) 로서의 티올 분자1) thiol molecule as internal standard for quantitative analysis
티올분자로 표면수식되는 다양한 형태의 나노/마이크로입자 (금, 은, 양자점, 산화철 등)를 이용한 연구에서 질량분석을 통해 검출하고자 하는 대상물질의 정확한 양을 측정하기 위한 내위 기준물질로 사용될 수 있다.In studies using various types of nano / microparticles (gold, silver, quantum dots, iron oxides, etc.) that are surface-modified with thiol molecules, they can be used as internal reference for measuring the exact amount of the target substance to be detected by mass spectrometry. .
2)다중 검지을 위한 티올 분자2) thiol molecule for multiple detection
티올분자로 표면수식되는 다양한 형태의 나노/마이크로입자 (금, 은, 양자점, 산화철 등)를 이용한 연구에서 질량분석을 이용한 다중검지 시스템에 이용될 수 있다.It can be used in multiple detection systems using mass spectrometry in studies using various types of nano / microparticles (gold, silver, quantum dots, iron oxides, etc.) surface-modified with thiol molecules.
본 발명을 통하여 알 수 있는 바와 같이, 본 발명의 중수소로 치환된 티올 분자는 질량분석 기준물질로 사용될 수 있으며, 여러 다양한 응용이 가능할 것이다.As can be seen from the present invention, the deuterated thiol molecule of the present invention can be used as a mass spectrometry reference material, and various various applications will be possible.
도 1은 에틸렌글리콜 한 유닛만 중수소로 치환된 분자의 합성과정을 나타낸 그림이고,
도 2는 에틸렌글리콜 두 유닛이상 중수소로 치환된 분자의 합성을 나타낸 그림이며,
도 3은 본 발명의 화합물들의 제조과정을 나타낸 모식도이고,
도 4는 NMR에 의한 반응 산물들을 규명한 그림으로, 4a는 2-(2-(2-(6-mercaptohexyloxy)ethoxy)ethoxy)ethanol-d4 (6-1, l=4, m=2, n=1), 4b는 2-(2-(2-(6-mercaptohexyloxy)ethoxy)ethoxy)ethanol-d8 (10-1, l=4, m=1, n=2,. 4c는 2-(2-(2-(6-mercaptohexyloxy)ethoxy)ethoxy)ethanol-d12 (10-3, l=4, m=0, n=3), 및 4d는 2-(2-(2-(11-mercaptoundecyloxy)ethoxy)ethoxy)ethanol-d4(6-2, l=9, m=2, n=1)이며,
도 5는 matrix 2-(2-(2-(6-mercaptohexyloxy)ethoxy)ethoxy)ethanol-d4 (6-1, l=4, m=2, n=1)를 사용한 MALDI-TOF MS에 의한 화학 구조의 특성화 그림이고,
도 6은 생성물 6인 2-(2-(2-(6-mercaptohexyloxy)ethoxy)ethoxy)ethanol-d4 (6-1, l=4, m=2, n=1)을 사용하여 생성된 금 나노입자 상에서 SAM의 질량 분석을 나타낸 그림이고,
도 7은 matrix 2-(2-(2-(6-mercaptohexyloxy)ethoxy)ethoxy)ethanol-d8 (10-1, l=4, m=1, n=2)를 사용한 MALDI-TOF MS에 의한 화학 구조의 특성화 그림이고,
도 8은 생성물 10인 2-(2-(2-(6-mercaptohexyloxy)ethoxy)ethoxy)ethanol-d8 (10-1, l=4, m=1, n=2)을 사용하여 생성된 금 나노입자 상에서 SAM의 질량 분석을 나타낸 그림이고,
도 9는 matrix 2-(2-(2-(6-mercaptohexyloxy)ethoxy)ethoxy)ethanol-d12 (10-3, l=4, m=0, n=3)를 사용한 MALDI-TOF MS에 의한 화학 구조의 특성화 그림이고,
도 10은 생성물 10인 2-(2-(2-(6-mercaptohexyloxy)ethoxy)ethoxy)ethanol-d12 (10-3, l=4, m=0, n=3)을 사용하여 생성된 금 나노입자 상에서 SAM의 질량 분석을 나타낸 그림이고,
도 11은 matrix 2-(2-(2-(11-mercaptoundecyloxy)ethoxy)ethoxy)ethanol-d4 (6-2, l=9, m=2, n=1)를 사용한 MALDI-TOF MS에 의한 화학 구조의 특성화 그림이고,
도 12는 생성물 6인 2-(2-(2-(11-mercaptoundecyloxy)ethoxy)ethoxy)ethanol-d4 (6-2, l=9, m=2, n=1)을 사용하여 생성된 금 나노입자 상에서 SAM의 질량 분석을 나타낸 그림이다.1 is a diagram showing the synthesis of molecules in which only one unit of ethylene glycol is substituted with deuterium,
2 is a diagram showing the synthesis of molecules substituted with deuterium at least two units of ethylene glycol,
Figure 3 is a schematic diagram showing the manufacturing process of the compounds of the present invention,
Figure 4 is a figure identifying the reaction products by NMR, 4a is 2- (2- (2- (6-mercaptohexyloxy) ethoxy) ethoxy) ethanol-d4 (6-1, l = 4, m = 2, n = 1), 4b is 2- (2- (2- (6-mercaptohexyloxy) ethoxy) ethoxy) ethanol-d8 (10-1, l = 4, m = 1, n = 2, .4c is 2- (2) -(2- (6-mercaptohexyloxy) ethoxy) ethoxy) ethanol-d12 (10-3, l = 4, m = 0, n = 3), and 4d is 2- (2- (2- (11-mercaptoundecyloxy) ethoxy) ethoxy) ethanol-d4 (6-2, l = 9, m = 2, n = 1),
Figure 5 Chemistry by MALDI-TOF MS using matrix 2- (2- (2- (6-mercaptohexyloxy) ethoxy) ethoxy) ethanol-d4 (6-1, l = 4, m = 2, n = 1) Is a characterization drawing of the structure,
FIG. 6 shows gold nanoparticles produced using
Figure 7 Chemistry with MALDI-TOF MS using matrix 2- (2- (2- (6-mercaptohexyloxy) ethoxy) ethoxy) ethanol-d8 (10-1, l = 4, m = 1, n = 2) Is a characterization drawing of the structure,
FIG. 8 shows gold nanoparticles produced using 2- (2- (2- (6-mercaptohexyloxy) ethoxy) ethoxy) ethanol-d8 (10-1, l = 4, m = 1, n = 2) as
Figure 9 Chemistry by MALDI-TOF MS using matrix 2- (2- (2- (6-mercaptohexyloxy) ethoxy) ethoxy) ethanol-d12 (10-3, l = 4, m = 0, n = 3) Is a characterization drawing of the structure,
FIG. 10 shows gold nanoparticles produced using 2- (2- (2- (6-mercaptohexyloxy) ethoxy) ethoxy) ethanol-d12 (10-3, l = 4, m = 0, n = 3) as
Figure 11 Chemistry by MALDI-TOF MS using matrix 2- (2- (2- (11-mercaptoundecyloxy) ethoxy) ethoxy) ethanol-d4 (6-2, l = 9, m = 2, n = 1) Is a characterization drawing of the structure,
FIG. 12 shows gold nanoparticles produced using
이하 비한정적인 실시예를 통하여 본 발명을 더욱 상세하게 설명한다. 단 하기 실시예는 본 발명을 예시하기 위한 의도로 기재된 것으로서 본 발명의 범위는 하기 실시예에 의하여 제한되는 것으로 해석되지 아니한다.The present invention will now be described in more detail by way of non-limiting examples. The following examples are intended to illustrate the invention and the scope of the invention is not to be construed as being limited by the following examples.
하기 실시예에서는 합성가능한 티올분자 중 대표적으로 l:m:n = 4:2:1인 경우와, l:m:n = 9:2:1인 경우의 두 티올분자에 대한 합성과정과, 두 최종물질의MMR과 결과를 제시한다.In the following examples, the synthesis process of two thiol molecules in the case of typically l: m: n = 4: 2: 1 and l: m: n = 9: 2: 1 of the synthesizable thiol molecules, Present the MMR of the final material and the results.
실시예Example 1:2-(2-( 1: 2- (2- ( hexhex -5--5- enyloxyenyloxy )) ethoxyethoxy )) ethanolethanol (2, l=4, m=2, n=0) 또는 2-(2-(undec-10-enyloxy)ethoxy)ethanol (l=9, m=2, n=0) 합성 (2, l = 4, m = 2, n = 0) or 2- (2- (undec-10-enyloxy) ethoxy) ethanol (l = 9, m = 2, n = 0) synthesis
NaOH (1.2 e.q.) 수용액 및 di-ethylene glycol(3 e.q.)의 혼합액을 100 ℃에서 1시간 교반한 후 6-bromohexene 또는 11-bromoundecene(1 e.q.)을 첨가하였다. 반응 혼합액을 밤새 교반하고 상온으로 냉각한 후 AcOEt로 추출하고 물, NH4Cl, brine으로 세척하고 MgSO4에서 건조하였다 그 결합된 유기 층을 농축하고 그 잔류물을 hexane : AcOEt(ethyl acetate) = 1:1로 실리카겔 젤 크로마토그래피로 정제하였다.
A mixture of NaOH (1.2 eq) aqueous solution and di-ethylene glycol (3 eq) was stirred at 100 ° C. for 1 hour, and 6-bromohexene or 11-bromoundecene (1 eq) was added thereto. The reaction mixture was stirred overnight, cooled to room temperature, extracted with AcOEt, washed with water, NH 4 Cl, brine and dried over MgSO 4. The combined organic layers were concentrated and the residue hexane: AcOEt (ethyl acetate) = Purification was carried out by silica gel gel chromatography at 1: 1.
실시예Example 2:6-(2-(2- 2: 6- (2- (2- bromoethoxybromoethoxy )) ethoxyethoxy )) hexhex -1--One- eneene (3, l=4, m=2, n=0) 또는 11-(2-(2-bromo- (3, l = 4, m = 2, n = 0) or 11- (2- (2-bromo- ethoxyethoxy )) ethoxyethoxy )) undecundec -1--One- eneene (l=9, m=2, n=0) (3)합성 (l = 9, m = 2, n = 0) (3) Synthesis
2 ml의 THF(tetrahydrofuran) 내의 상기 화합물 2의 용액에 triphenyl phosphine(Ph3P) (1.5 e.q.)를 첨가하였다. 그 반응 혼합물을 상온에서 교반하고 carbontetrabromide(1.5 e.q.)을 첨가하고 상온에서 5시간 동안 교반하였다. 그 반응 혼합물을 헥산으로 여과하였다. 그 유기 층을 농축하고 그 잔류물을 hexane : AcOEt = 20:1로 실리카겔 젤 크로마토그래피로 정제하였다.
To the solution of
실시예Example 3:2-(2-(2-( 3: 2- (2- (2- ( hexhex -5--5- enyloxyenyloxy )) ethoxyethoxy )) ethoxyethoxy )) ethanolethanol -- d4d4 (4, l=4, m=2, n=1) 또는 2-(2-(2-( (4, l = 4, m = 2, n = 1) or 2- (2- (2- ( undecundec -10--10- enyloxyenyloxy )) ethoxyethoxy )) ethoxyethoxy )) ethanolethanol -- d4d4 (l=9, m=2, n=1) (4)합성 (l = 9, m = 2, n = 1) (4) Synthesis
600 ul의 DMF 내의 상기 화합물 3의 용액에 NaH (1.45 e.q.)를 0 ℃에서 첨가하였다. 그 반응 혼합물을 상온에서 1시간 동안 교반하고 ethyleneglycol-D4 (3.6 e.q.)을 첨가하고 상온에서 밤새 교반하였다. 그 반응 혼합물을 TDW로 중지하고 물, NH4Cl, brine으로 세척하고 MgSO4에서 건조하였다 그 유기 층을 농축하고 그 잔류물을 hexane : AcOEt = 3:1로 실리카겔 젤 크로마토그래피로 정제하였다.To a solution of
실시예Example 4: S-6-(2-(2-(2- 4: S-6- (2- (2- (2- hydroxyethoxyhydroxyethoxy )) ethoxyethoxy )) ethoxyethoxy )) hexylhexyl ethanethioateethanethioate -- d4d4 (5, m=4, m=2, n=1) 또는 S-11-(2-(2-(2- (5, m = 4, m = 2, n = 1) or S-11- (2- (2- (2- hydroxyethoxyhydroxyethoxy )) ethoxyethoxy )) ethoxyethoxy )) undecylundecyl ethanethioate (l=9, m=2, n=1) (5)합성 ethanethioate (l = 9, m = 2, n = 1) (5) Synthesis
상기 화합물 4를 7 ml의 MeOH에 녹였다. Thioacetic acid (4 e.q.)를 첨가하고 한 스패툴라의 AMPA를 수반하였다. 그 반응 혼합물을 N2 분위기하에서 밤새 재환류(reflux)하기 위하여 가열하였다. 그 반응 혼합물을 농축하고 그 잔류물을 AcOEt 하에서 취하고,물, NH4Cl, brine으로 세척하고 MgSO4에서 건조하였다 그 혼합물을 농축하고 그 잔류물을 hexane : AcOEt = 3:1로 실리카겔 젤 크로마토그래피로 정제하였다.
실시예Example 5:2-(2-(2-(6- 5: 2- (2- (2- (6- mercaptohexyloxymercaptohexyloxy )) ethoxyethoxy )) ethoxyethoxy )) ethanolethanol -- d4d4 (6, l=4, m=2, n=1) 및 2-(2-(2-(11-mercaptoundecyloxy)ethoxy)ethoxy)ethanol (l=9, m=2, n=1) (6)합성 (6, l = 4, m = 2, n = 1) and 2- (2- (2- (11-mercaptoundecyloxy) ethoxy) ethoxy) ethanol (l = 9, m = 2, n = 1) (6) synthesis
상기 화합물 5를 7 ml의 MeOH에서 녹인 후 HCl를 그 반응 혼합물에 첨가한 후 밤새 재환류를 위하여 가열하였다. 반응 후, 그 반응 혼합물을 농축하고 그 잔류물을 AcOEt 하에서 취하고,물, NH4Cl, brine으로 세척하고 MgSO4에서 건조하고 여과하였다. 그 혼합물을 농축하고 hexane : AcOEt = 1:4로 실리카겔 젤 크로마토그래피로 정제하였다.
실시예Example 5: 5: MALDIMALDI -- TOFTOF MS( MS ( matrixmatrix assistedassisted laserlaser desorptiondesorption / Of ionizationionization timetime ofof flight flight massmass spectrometryspectrometry )에 의한 중수소로 치환된 Deuterated by 알칸분자의Alkanes 특성화 Specialization
질량 분석을 이온화 원으로 스마트 빔 레이져를 구비한 Autoflex III MALDI-TOF mass spectrometer (Bruker Daltonics, Germany)를 사용하여 수행하였다. 모든 스펙트럼을 19 kV 가속 전압, 100 Hz 반복률, 및 평균 ~700shots으로 얻었다. 분석체를 매트릭스로 THAP (5 mg/mL in acetonitrile)을 사용하거나 금 나노입자 상에 자가 조립된(self-assembled) 단층 형성 후 직접적으로 특성화하였다.Mass spectrometry was performed using an Autoflex III MALDI-TOF mass spectrometer (Bruker Daltonics, Germany) with a smart beam laser as the ionization source. All spectra were obtained with 19 kV acceleration voltage, 100 Hz repetition rate, and average ˜700shots. The analytes were characterized directly using THAP (5 mg / mL in acetonitrile) as the matrix or after self-assembled monolayer formation on gold nanoparticles.
도 5에서 도 12에서 알 수 있는 바와 같이, 본 발명의 화합물을 이용하여 합성된 분자의 확인을 위해 질량분석을 수행하여 예측했던 분자량을 얻었다. 또, 합성된 분자들이 금표면위에서 제대로 자기조립단분자층을 형성한 후 질량분석기로 분석되는지 여부를 확인하였고 예측된 분자량을 얻었다. 이 결과는 이 분자의 사용예시에서 제시한 바와 같이 질량분석을 통한 미세분자의 다중검지 시스템을 통한 검출에 이용될 수 있다는 걸 증명한다.As can be seen in FIG. 5 to FIG. 12, mass spectrometry was performed to confirm the molecular weight synthesized using the compound of the present invention to obtain a predicted molecular weight. In addition, it was confirmed whether the synthesized molecules were properly analyzed on a gold surface by mass spectrometry and then analyzed by mass spectrometry to obtain the predicted molecular weight. This result demonstrates that it can be used for the detection of multiple molecules of micromolecules through mass spectrometry, as shown in the use example of this molecule.
Claims (6)
[화학식 1]
여기서, l은 0~9의 정수, m은 0 이상의 정수이고, n은 1 이상의 정수이며, m과 n의 합은 3, 4, 5 또는 6임.Thiol molecules substituted with deuterium as described in Formula 1:
[Formula 1]
Here, l is an integer of 0-9, m is an integer of 0 or more, n is an integer of 1 or more, and the sum of m and n is 3, 4, 5 or 6.
b)상기 2-(2-(hex-5-enyloxy)ethoxy)ethanol 또는 2-(2-(undec-10-enyloxy)ethoxy)ethanol에 트리페닐 포스핀(triphenyl phosphine) 첨가하여 교반하고 카본테트라브로마이드(carbontetrabromide)를 첨가하고 반응시켜서 6-(2-(2-bromoethoxy)ethoxy)hex-1-ene 또는 11-(2-(2-bromo- ethoxy)ethoxy)undec-1-ene 을 합성하는 단계;
c)6-(2-(2-bromoethoxy)ethoxy)hex-1-ene 또는 11-(2-(2-bromo- ethoxy)ethoxy)undec-1-ene 용액에 NaH 및 에틸렌글리콜-D4를 첨가하고 반응시켜서 2-(2-(2-(hex-5-enyloxy)ethoxy)ethoxy)ethanol-d4 또는 2-(2-(2-(undec-10-enyloxy)ethoxy)ethoxy)ethanol-d4를 합성하는 단계;
d)2-(2-(2-(hex-5-enyloxy)ethoxy)ethoxy)ethanol-d4 또는 2-(2-(2-(undec-10-enyloxy)ethoxy)ethoxy)ethanol-d4 용액에 티오아세트산(Thioacetic acid) 및 AMPA(2,2'-azobis(2-methylpropionamidine)dihydrochloride)를 가하고 반응시켜서 S-6-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)hexyl ethanethioate-d4 또는 S-11-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)undecyl ethanethioate를 합성하는 단계;및
e)S-6-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)hexyl ethanethioate-d4 또는 S-11-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)undecyl ethanethioate 용액에 HCl를 첨가하여 반응한 후 정제하여 2-(2-(2-(6-mercaptohexyloxy)ethoxy)ethoxy)ethanol-d4 또는 2-(2-(2-(11-mercaptoundecyloxy)ethoxy)ethoxy)ethanol을 합성하는 단계를 포함하는 하기 화학식 1의 화합물 제조방법;
[화학식 1]
여기서, l은 0~9의 정수, m은 0 이상의 정수이고, n은 1 이상의 정수이며, m과 n의 합은 3, 4, 5 또는 6임.a) 2- (2- (hex-5-enyloxy) ethoxy) ethanol or 2 by adding 6-bromohexene or 11-bromooundecene to the mixed solution of NaOH solution and diethylene glycol and reacting Synthesizing-(2- (undec-10-enyloxy) ethoxy) ethanol;
b) triphenyl phosphine was added to 2- (2- (hex-5-enyloxy) ethoxy) ethanol or 2- (2- (undec-10-enyloxy) ethoxy) ethanol, followed by stirring and carbon tetrabromide adding (carbontetrabromide) and reacting to synthesize 6- (2- (2-bromoethoxy) ethoxy) hex-1-ene or 11- (2- (2-bromoetheth) ethoxy) undec-1-ene;
c) Add NaH and ethylene glycol-D4 to a 6- (2- (2-bromoethoxy) ethoxy) hex-1-ene or 11- (2- (2-bromoethoxy) ethoxy) undec-1-ene solution Reacting to synthesize 2- (2- (2- (hex-5-enyloxy) ethoxy) ethoxy) ethanol-d4 or 2- (2- (2- (undec-10-enyloxy) ethoxy) ethoxy) ethanol-d4 step;
d) 2- (2- (2- (2- (hex-5-enyloxy) ethoxy) ethoxy) ethanol-d4 or 2- (2- (2- (undec-10-enyloxy) ethoxy) ethoxy) ethanol-d4 in solution Acetic acid (Thioacetic acid) and AMPA (2,2'-azobis (2-methylpropionamidine) dihydrochloride) are added and reacted to give S-6- (2- (2- (2-hydroxyethoxy) ethoxy) ethoxy) hexyl ethanethioate-d4 or S Synthesizing -11- (2- (2- (2-hydroxyethoxy) ethoxy) ethoxy) undecyl ethanethioate; and
e) HCl in S-6- (2- (2- (2-hydroxyethoxy) ethoxy) ethoxy) hexyl ethanethioate-d4 or S-11- (2- (2- (2- (2-hydroxyethoxy) ethoxy) ethoxy) undecyl ethanethioate solution After the reaction was carried out to purify to synthesize 2- (2- (2- (6-mercaptohexyloxy) ethoxy) ethoxy) ethanol-d4 or 2- (2- (2- (11-mercaptoundecyloxy) ethoxy) ethoxy) ethanol Method for preparing a compound of formula (1) comprising the step;
[Formula 1]
Here, l is an integer of 0-9, m is an integer of 0 or more, n is an integer of 1 or more, and the sum of m and n is 3, 4, 5 or 6.
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